A new class of pentapeptide KISS1 receptor agonists with hypothalamic–pituitary–gonadal axis activation

The kisspeptin (Kp, Kp-54, metastin)/KISS1R system plays crucial roles in regulating the secretion of gonadotropin-releasing hormone. Continuous administration of nonapeptide Kp analogs caused plasma testosterone depletion, whereas bolus administration caused strong plasma testosterone elevation in male rats. To develop a new class of small peptide drugs, we focused on stepwise N-terminal truncation of Kp analogs and discovered potent pentapeptide analogs. Benzoyl-Phe-azaGly-Leu-Arg(Me)-Trp-NH₂ (16) exhibited high agonist activity for KISS1R and excellent metabolic stability in rat serum. A single injection of a 4-pyridyl analog (19) at the N-terminus of 16 into male Sprague Dawley rats caused a robust increase in plasma luteinizing hormone levels, but unlike continuous administration of nonapeptide Kp analogs, continuous administration of 19 maintained moderate testosterone levels in rats. These results indicated that small peptide drugs can be successfully developed for treating sex hormone deficiency.     

Trophic polymorphism in bluegill sunfish (<Emphasis Type="Italic">Lepomis macrochirus</Emphasis>) introduced into Lake Biwa: evidence from stable isotope analysis

Trophic polymorphism was recently reported in introduced bluegill (Lepomis macrochirus) in Lake Biwa, Japan, where three morphs are specialized in benthic invertebrates (benthivorous type), submerged aquatic plants (herbivorous type), and zooplankton (planktivorous type). We evaluated the long-term effects of food resource utilization by these trophic morphs using stable isotope ratios, δ¹⁵N and δ¹³C. A significant difference in δ¹⁵N was found between the benthivorous and planktivorous types. The planktivorous type had the higher δ¹⁵N value, which corresponded with the value expected from its prey, zooplankton. The lower δ¹⁵N value of the benthivorous type would be derived from the lower δ¹⁵N values of benthic prey organisms compared to zooplankton. These results support previous findings that the benthivorous and planktivorous types have different food resource utilization. In contrast, the δ¹⁵N and δ¹³C values of the herbivorous type were distinctly different from the expected values, indicating that this type was unlikely to utilize aquatic plants substantially, contradicting the results of the dietary analysis.     

Makomotindoline from Makomotake, Zizania latifolia infected with Ustilago esculenta

Makomotindoline (1) was isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta. The structure was determined by the interpretation of spectroscopic data and synthesis. Makomotindoline (1), its l-Glc isomer (2) and its aglycon (3) were synthesized and their effects on rat glioma cells showed adverse effects on the cell growth.     

UV protection in the photosymbiotic ascidian Didemnum molle inhabiting different depths

Didemnum molle is a colonial ascidian that harbors the prokaryotic photosymbiont Prochloron in its cloacal cavity. Colonies occur over a relatively wide bathymetric range (approximately 0-30 m), and colony color is widely variable, partly depending on depth. Colonies in shallow sites are bright white, with densely distributed spicules, and often with brown or dark gray pigmentation, while colonies in deeper sites are less pigmented, with sparsely distributed spicules. Didemnum molle colonies contain mycosporine-like amino acids (MAAs) as UV-absorbing substances. These include mycosporine-glycine, shinorine, and porphyra-334. Among colonies from 5-, 10-, 15-, and 20-m depths, the concentration of total MAAs was significantly high at 10 m and low at 20 m. Colonies at 10 m need to maintain low spicule densities to have enough photosynthetically active radiation (PAR) to maintain the photosymbionts, and they probably concentrate MAAs to block UV radiation without attenuating PAR. Because high levels of PAR cause photoinhibition of photosynthesis, spicules and pigment cells would be more effective for photoprotection in shallow water. Colonies of D. molle may adjust the light conditions for photosymbionts by combining MAAs, spicules, and pigment cells in varying amounts.     

Stable knock-down of vomeronasal receptor genes in transgenic Xenopus tadpoles

Xenopus V2R (xV2R), a family of G-protein-coupled receptors with seven transmembrane domains, is expressed in the Xenopus vomeronasal organ (VNO). There are six subgroups of xV2R, one of which, xV2RE, is predominantly expressed in the VNO. To understand the function of xV2R during VNO development, we developed a new method to achieve stable siRNA-suppression of the V2RE genes by introducing siRNA expression transgenes into the genomes of unfertilized eggs. We found that some of the derived transgenic tadpoles lacked VNOs and that their olfactory epithelium was fused. With the exception of one tadpole, expression of xV2RE was not detected in morphologically abnormal mutant tadpoles, although the olfactory marker protein and the olfactory receptors were expressed. These results suggest that we successfully produced transgenic tadpoles in which xV2RE expression was stably suppressed by siRNA, and that xV2RE plays a role in the morphogenesis of olfactory organs.     

Intra-strain polymorphisms are detected but no genomic alteration is found in cloned mice

In-gel competitive reassociation (IGCR) is a method for differential subtraction of polymorphic (RFLP) DNA fragments between two DNA samples of interest without probes or specific sequence information. Here, we applied the IGCR procedure to two cloned mice derived from an F1 hybrid of the C57BL/6Cr and DBA/2 strains, in order to investigate the possibility of genomic alteration in the cloned mouse genomes. Each of the five of the genomic alterations we detected between the two cloned mice corresponded to the "intra-strain" polymorphisms in the C57BL/6Cr and DBA/2 mouse strains. Our result suggests that no severe aberration of genome sequences occurs due to somatic cell nuclear transfer.     

Conserved origin of the ventral pancreas in chicken

To determine the origin of the ventral pancreas, a fate map of the ventral pancreas was constructed using DiI crystal or CM-DiI to mark regions of the early chick endoderm: this allowed correlations to be established between specific endoderm sites and the positions of their descendants. First, the region lateral to the 7- to 9-somite level, which has been reported to contribute to the ventral pancreas, was shown to contribute mainly to the intestine or the dorsal pancreas. At the 10 somite stage (ss), the ventral pre-pancreatic cells reside laterally at the 2-somite level, at the lateral boarder of the somite. At this stage, however, the fate of these cells has not yet segregated and they contribute to the ventral pancreas and to the intestine or bile duct. The ventral pancreas fate segregated at the 17 ss; the cells residing at the somite boarder at the 4-somite level at the 17 ss were revealed to contribute to the ventral pancreas. Interestingly, the dorsal and the ventral pancreatic buds are different in both origin and function. These two pancreatic buds begin to fuse at day 7 (HH 30) of embryonic development. However, whereas the dorsal pancreas gives rise to both Insulin-expressing endocrine and Amylase-expressing exocrine cells, the ventral pancreas gives rise to Amylase-expressing exocrine cells, but not insulin-expressing endocrine cells before day 7 (HH 30) of embryonic development.